Nuclear RNA surveillance of genome expression: From yeast to mammals

基因组表达的核 RNA 监测：从酵母到哺乳动物

• 批准号: BB/F010273/1
• 负责人: Nicholas Proudfoot
• 金额: $ 32.74万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF010273%2F1
• 关键词: Nuclear; RNA; surveillance; genome; expression

The successful production of proteins from their gene blueprint (DNA) requires a key intermediate step in which a particular gene is selected by complex molecular machines and initially copied into a related RNA molecule called the transcript. However this process is far more complex than initially predicted as much of the RNA transcript does not directly encode protein and is referred to as non-coding RNA. Surprisingly gene transcripts are predominantly non-coding so that the protein coding portions must be joined together forming so called messenger RNA with the non-coding (intronic) RNA chopped out by a process called RNA splicing. Indeed splicing can occur in different ways so that many different messenger RNAs can be generated from just one initial RNA transcript. We have shown that non-coding RNA is first removed from the gene transcript before splicing occurs and at the same time that the transcript is being synthesised. Thus non-coding RNA can be sorted out and removed before critical splicing events take place. This seemingly wasteful mechanism is not only employed to help make the process of messenger RNA production more efficient and better regulated but is also used to completely degrade any messenger RNAs that might have protein coding defects. Removal of such mutant messenger RNAs is likely to be a critical quality control mechanism to prevent the synthesis of the wrong protein which in turn could have damaging effects on cell function. This mechanism is now given the name of Nuclear RNA Surveillance (NuRNASu). In the absence of this intricate quality control process cells will become deregulated leading to diseases such as cancer.

从基因蓝图（DNA）成功生产蛋白质需要一个关键的中间步骤，在这个步骤中，一个特定的基因被复杂的分子机器选择，并最初复制到一个相关的RNA分子中，称为转录本。然而，这个过程比最初预测的要复杂得多，因为大部分RNA转录物不直接编码蛋白质，被称为非编码RNA。令人惊讶的是，基因转录物主要是非编码的，因此蛋白质编码部分必须连接在一起形成所谓的信使RNA，其中非编码（内含子）RNA通过称为RNA剪接的过程被切断。事实上，剪接可以以不同的方式发生，因此可以从一个初始RNA转录物产生许多不同的信使RNA。我们已经证明，非编码RNA首先从基因转录本中去除，然后剪接发生，同时转录本正在合成。因此，非编码RNA可以在关键剪接事件发生之前被分选出来并去除。这种看似浪费的机制不仅用于帮助使信使RNA的生产过程更有效和更好地调节，而且还用于完全降解任何可能具有蛋白质编码缺陷的信使RNA。去除这种突变信使RNA可能是一种关键的质量控制机制，以防止合成错误的蛋白质，这反过来可能对细胞功能产生破坏性影响。这种机制现在被命名为核RNA监视（NuRNASu）。如果没有这种复杂的质量控制过程，细胞将变得失调，导致癌症等疾病。